A model for the study of skeletal anomalies in rat fetuses

Effting, Cristiane; Paula, Daniel Jesus de; Nunes, Guilhermino Pereira

doi:10.1590/s1516-89132004000100005

Cited by 4 publications

(7 citation statements)

References 8 publications

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“…21 –23 Furthermore, clinical studies evaluating the safety of artemisinins also reported conflicting data regarding the first-trimester exposure but found no adverse effects in the second or third trimester. 19…”

Section: Discussionmentioning

confidence: 99%

Teratogenicity of Artemether–Clindamycin Nanostructured Lipid Carriers in Rats

et al. 2016

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Currently, artemisinin-based combination therapy is considered the best option in the treatment of malaria. However, toxicity of artemisinins limits their use in pregnancy. In the absence of sufficient toxicity data, the World Health Organization recommends that artemisinins are not to be used in the first trimester of pregnancy and can be used only in second and third trimesters, when other treatments are not available. We have recently observed that drugs loaded in nanolipid carriers are selectively taken up in Plasmodium-infected erythrocytes with a concomitant reduction in the dose required to cure animals. Thus, 20% of the therapeutic dose of artemether-clindamycin (ARM-CP) loaded in nanostructured lipid carriers (NLCs; mean particle size 55 ± 10 nm) resulted in complete parasite clearance and 100% survival of infected mice. Here, we investigate the teratogenicity of this formulation in rodents (dosing on alternate days from 6th day to 18th day of gestation; 12-15 animals/group). The teratogenicity of drug-free NLCs and artesunate-clindamycin (ARS-CP) solution was also evaluated. We found that the therapeutic dose of ARS-CP caused fetal resorptions (87.5% resorptions in 8 litters), suggesting its unsuitability for use in pregnancy. Artesunate-clindamycin NLCs at therapeutic doses also resulted in ∼90% fetal resorptions in 10 litters examined. However, postimplantation losses or fetal malformations were not observed at the dose of ARM-CP NLCs that was required for complete parasite clearance in preclinical trials (ie, 20% of the therapeutic dose). Our data suggest that the NLCs loaded with 20% of the therapeutic dose of ARM-CP may have potential in treating malaria during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Teratogenicity of Artemether–Clindamycin Nanostructured Lipid Carriers in Rats

et al. 2016

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“…Resorption was classified "early" when only placental tissue was visible and "late" when placenta as well as embryonic tissue was visible. Fetuses were cleared with KOH and stained with alizarin red (Manson et al, 1982;Effting et al, 2004) and examined under a dissecting microscope. Skeletal anomalies were analyzed according to a modified method of Manson et al (1982).…”

Section: Methodsmentioning

confidence: 99%

Ketoconazole- and fluconazole-induced embryotoxicity and skeletal anomalies in wistar rats: a comparative study

Amaral

Nunes

2008

Braz. arch. biol. technol.

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Ketoconazole and fluconazole are two broad-spectrum azole antifungals used for the treatment of superficial and systemic mycoses. Embryotoxicity and teratogenicity have been reported in some studies when those drugs are administered at high doses to pregnant rats. The aim of this study was to present a comparative study of embryotoxic effects as well as the skeletal anomalies in fetuses of Wistar rats which received ketoconazole and fluconazole at teratogenic doses on gestational days (GD) 6 through 15 (organogenesis period). On gestational day (GD) 21, the dams were euthanized and examined for standard parameters of reproductive outcome. Fetuses were stained with alizarin red and the bones of the head, trunk, forelimb and hindlimb were examined for detection of skeletal anomalies. The frequency of skeletal anomalies in the ketoconazole-treated group was significant when compared to the fluconazole and the control group.
O cetoconazol e o fluconazol são dois antifúngicos azólicos, de amplo espectro, utilizados no tratamento de micoses superficiais e sistêmicas. Alguns estudos relatam a embriotoxicidade e teratogenicidade induzidas por estes fármacos quando os mesmos são administrados em altas doses a ratas prenhes. O objetivo deste trabalho foi apresentar um estudo comparativo dos efeitos embriotóxicos e das anomalias esqueléticas em fetos de ratas Wistar que receberam cetoconazol e fluconazol em doses teratogênicas do 6º ao 15º dia gestacional (GD) (período da organogênese). No 21º GD as ratas foram eutanaziadas e examinadas quanto aos parâmetros padrões de performance reprodutiva. Os fetos foram corados com vermelho de alizarina e os ossos da cabeça, do tronco e dos membros anteriores e posteriores foram examinados para a verificação de anomalias esqueléticas. A freqüência de anomalias esqueléticas no grupo tratado com cetoconazol foi significante quando comparada à dos grupos fluconazol e controle

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“…Penentuan dosis terendah pemajanan endosulfan pada penelitian ini didasarkan pada penelitian Paramita (2010), sedangkan dosis tertinggi didasarkan pada penelitian Singh et al (2007). Pemajanan dilakukan secara oral menggunakan sonde lambung selama 10 hari berturut-turut pada periode organogenesis yaitu umur kebuntingan 6-15 hari (Effting et al, 2004). Pada umur kebuntingan 20 hari, hewan uji dikorbankan nyawanya dengan cara dislokasio leher, lalu dibedah untuk diamati tampilan reproduksi dan malformasi rangka pada fetus.…”

Section: Metode Penelitianunclassified

“…Data pengamatan efek teratogenik terhadap malformasi rangka fetus dilakukan dengan menghitung jumlah fetus yang mengalami kelainan pada kelompok pemajanan endosulfan dibandingkan dengan kelompok kontrol. Perbedaan sigifikansinya diuji dengan uji eksak Fisher pada taraf kepercayaan 95% (Effting et al, 2004). Semua analisis data dilakukan dengan menggunakan program SPSS untuk Windows Versi 18.0.0 (SPSS, Inc., Chicago, IL, USA).…”

Section: Analisis Dataunclassified

“…Pengamatan efek teratogenik terhadap pembentukan rangka dimulai dengan membuat sediaan Wholemount dari rangka fetus, menggunakan metode pewarnaan Alizarin red S dengan modifikasi, berdasarkan Effting et al (2004) (2012), endosulfan dapat mengganggu sistem reseptor progesteron, sehingga dapat meningkatkan risiko keguguran. Guyton (1976), menyatakan bahwa progesteron merupakan hormon yang berperan penting dalam proses kebuntingan karena progesteron menyebabkan sel-sel penyusun desidua berkembang pada endometrium, dan sel ini memegang peranan penting dalam proses pemberian nutrisi pada embrio pada tahap awal perkembangan.…”

Section: Pengamatan Efek Teratogenik Endosufan Pada Pembentukan Rangkunclassified

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Malformasi Rangka Fetus Tikus Wistar Akibat Efek Teratogenik Insektisida Endosulfan (SKELETAL MALFORMATION OF WISTAR RAT FETUSES DUE TO THE TERATOGENIC EFFECT OF ENDOSULFAN INSECTICIDE)

Malini¹,

Madihah²,

Shalihah³

2017

JVet

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Endosulfan an organochlorine insecticide that is commonly used even though it has been banned due to its toxic and teratogenic effect. This study aims to determine the effect of orally endosulfan exposure to pregnant rat (Rattus norvegicus) at day 6-15th of gestation period to the foetus skeletal malformation. A Completely Randomized Design (CRD) by endosulfan dosages: 0 (control); 0.083; 0.190; 0.440; 1.000 mg/kg BW/day with 5 replicates was applied. At 20th of the gestational period, the rats were sacrificed, their reproductive organs and the fetal skeletal malformation were observed using Alizarin red S method. The results of one-way ANOVA test showed that endosulfan exposure did not significantly affect the pregnancy outcomes ie. female rats weight gain, the numbers of implanted foetus, foetal body weight and length, respectively. Malformation of foetus implantation, foetus size and foetus skeletal occured in the endosulfan exposure groups. Fisher’s exact test results showed a significant difference between the control group and the endosulfan exposure group on the number of foetuses that have abnormalities in the number of skeletons of the sternum, fore and hind paws. The exposure of endosulfan at 0.083-1.000 mg / kg BW / day in pregnant rats caused skeletal malformations of the foetus ie. decreased in the number on sternum, fore- and hind paw bones. ABSTRAK Endosulfan merupakan insektisida golongan organoklorin yang masih digunakan hingga kini meski telah dilarang karena bersifat toksik dan teratogenik. Penelitian ini bertujuan untuk mengetahui efek pemajanan endosulfan secara oral terhadap malformasi rangka fetus tikus (Rattus norvegicus Berkenhout, 1769) selama umur kebuntingan 6-15 hari. Penelitian dilakukan secara eksperimental di laboratorium menggunakan Rancangan Acak Lengkap (RAL) dengan pemajanan endosulfan dosis: 0 (kontrol); 0,083; 0,19; 0,44; dan 1 mg/kg BB/hari dan masing-masing diulang sebanyak lima kali. Induk betina dengan umur kebuntingan 20 hari, dikorbankan nyawanya lalu dibedah dan diamati tampilan reproduksi induk serta malformasi rangka pada fetus dengan metode pewarnaan Alizarin red S. Hasil uji sidik ragam satu arah menunjukkan pemajanan endosulfan tidak berpengaruh secara signifikan terhadap rataan pertambahan bobot badan induk, jumlah fetus terimplantasi, bobot badan dan panjang fetus. Malformasi implantasi fetus, ukuran fetus dan rangka fetus terjadi pada kelompok pemajanan endosulfan. Hasil uji eksak Fisher menunjukkan adanya perbedaan yang signifikan antara kelompok kontrol dengan kelompok pemajanan endosulfan terhadap jumlah fetus yang mengalami kelainan jumlah rangka penyusun sternum, cakar depan dan cakar belakang. Simpulan dari penelitian ini adalah pemajanan endosulfan dosis 0,083- 1,000 mg/kg BB/hari pada tikus bunting menimbulkan malformasi rangka pada fetus yaitu berkurangnya jumlah tulang penyusun sternum, cakar depan, dan cakar belakang.

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A model for the study of skeletal anomalies in rat fetuses

Abstract: ABSTRACT

Cited by 4 publications

References 8 publications

Teratogenicity of Artemether–Clindamycin Nanostructured Lipid Carriers in Rats

Teratogenicity of Artemether–Clindamycin Nanostructured Lipid Carriers in Rats

Ketoconazole- and fluconazole-induced embryotoxicity and skeletal anomalies in wistar rats: a comparative study

Malformasi Rangka Fetus Tikus Wistar Akibat Efek Teratogenik Insektisida Endosulfan (SKELETAL MALFORMATION OF WISTAR RAT FETUSES DUE TO THE TERATOGENIC EFFECT OF ENDOSULFAN INSECTICIDE)

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